A large number of children are chronically exposed to high levels of ambient air pollutants. Acute respiratory effects from ambient levels are well documented; however, effects from chronic exposures have not been as extensively studied. We are conducting a prospective cohort study (Children's Health Study (CHS)), designed to determine the respiratory health effects of chronic exposure to ambient air pollution among children and adolescents in 12 southern California communities. Preliminary results from this study indicate that chronic exposure to air pollutants decreases the rate of lung function growth and increases the frequency and severity of respiratory illnesses. Intraindividual variations in the magnitude of effects suggest that some children may be more susceptible to air pollutants than others. Diet and genetic factors, as well as age, and health status, may affect susceptibility. We propose to determine whether 1) dietary intake of fruits, vegetables and antioxidant nutrients, and 2) polymorphisms in genes involved in lung defenses (GSTM1, GSTT1, GSTP1, MPO, TNFa) modify the effect of air pollution on respiratory health. These aims will be accomplished by assessing diet and genotypes of participants in the CHS, the ongoing prospective cohort study. The CHS collects annual pulmonary function tests, extensive data for modeling total personal exposures, annual questionnaire-based data on symptoms and respiratory illnesses, and data on the occurrence of respiratory illnesses using a school absence monitoring system. To assess variation in susceptibility, we will recruit all active CHS cohort members (2500) and graduates from the CHS (500), collect dietary intake data using Harvard University's Youth/Adolescent Questionnaire, a food frequency questionnaire designed and validated for older children, and add a laboratory component for genotyping using tested methods for collection of buccal cells and RFLP/PCR assays. Questionnaire-based data will be collected during school visits for active cohort members and by mail for graduates. Self-reported physician diagnoses and hospitalizations for respiratory illnesses will be validated. Findings from this study have the potential to refine knowledge of the dose-response relationship for air pollutants and improve strategies to prevent their adverse respiratory effects.